Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

In a normally functioning heart, blood is pumped through the aortic valve (the "gatekeeper" of the heart) and out of the aorta to the rest of the body. Aortic valve stenosis (AS) is the third leading cause of adult heart disease and the most common form of acquired valvular disease in developed countries. Although some AS risk factors are known, the true interactions are complex and involve age, lifestyle factors, and genetics. Many different genes likely affect the development of these conditions. For each gene involved, there can be a variety of slight differences, or variants, known as single nucleotide polymorphisms (SNPs), in the DNA sequence of a gene. We are using an efficient and cost-effective multi-stage strategy to detect genetic variants associated with AS. We have genotyped over 1 million SNPs across the genome in AS patients (cases) and individuals without AS (controls) using separately pooled case and control DNA samples. Genotyping the individual case and control samples, as well as testing our results in a separate population will be necessary to verify the association of these SNPs with AS. Discovery of AS susceptibility genes holds the promise to provide critical insights into the mechanisms of AS, potentially leading to development of new molecular targets for therapeutics, as well as early detection of at-risk persons and new preventive measures for this serious valvular disease.